Background: RAISE-XT (NCT04225871; Phase 3 study) showed clinically meaningful and sustained improvements in myasthenia gravis (MG)-specific outcomes with zilucoplan, a macrocyclic peptide complement component 5 inhibitor, in patients with acetylcholine receptor autoantibody-positive generalised MG. Methods: Adults self-administered once-daily subcutaneous zilucoplan 0.3mg/kg. This post hoc analysis assessed durability of response to Week 120 in MG-Activities of Daily Living (MG-ADL) and Quantitative MG (QMG) responders at Week 1 of two double-blind studies (NCT03315130, NCT04115293). Responder definitions: improvements of ≥3-points (MG-ADL) or ≥5-points (QMG) (interim data cut: 11 November 2023). Results: 93 patients were randomised to zilucoplan 0.3mg/kg in the double-blind studies; 43.0% (n=40/93) and 33.3% (n=31/93) were MG-ADL and QMG responders, respectively, at Week 1. Week 1 responders spent a median #of 98.9% (5.8–99.2) and 99.0% (2.5–99.2) time in response up to Week 120 for MG-ADL and QMG. Week 1 non-responders spent# a median #of 84.6% (0.0–98.3) and 66.7% (0.0–98.9) time in response up to Week 120 for MG-ADL and QMG, with most responding later in the study. Conclusions: Among early (Week 1) zilucoplan responders, time in response remained high (99%) up to Week 120. These data demonstrate rapid and sustained efficacy with long-term zilucoplan treatment.#

Background: Deep brain stimulation (DBS) in Parkinson’s disease (PD) requires extensive trial-and-error programming, often taking over a year to optimize. An objective, rapid biomarker of stimulation success is needed. Our team developed a functional magnetic resonance imaging (fMRI)-based algorithm to identify optimal DBS settings. This study prospectively compared fMRI-guided programming with standard-of-care (SoC) clinical programming in a double-blind, crossover, non-inferiority trial. Methods: Twenty-two PD-DBS patients were prospectively enrolled for fMRI using a 30-sec DBS-ON/OFF cycling paradigm. Optimal settings were identified using our published classification algorithm. Subjects then underwent >1 year of SoC programming. Clinical improvement was assessed under SoC and fMRI-determined stimulation conditions. Results: fMRI optimization significantly reduced the time required to determine optimal settings (1.6 vs. 5.6 months, p<0.001). Unified Parkinson’s Disease Rating Scale (UPDRSIII) improved comparably with both approaches (23.8 vs. 23.6, p=0.9). Non-inferiority was demonstrated within a predefined margin of 5 points (p=0.0018). SoC led to greater tremor improvement (p=0.019), while fMRI showed greater bradykinesia improvement (p=0.040). Conclusions: This is the first prospective evaluation of an algorithm able to suggest stimulation parameters solely from the fMRI response to stimulation. It suggests that fMRI-based programming may achieve equivalent outcomes in less time than SoC, reducing patient burden while potentially enhancing bradykinesia response.

Background: Vasospasm is an important complication of subarachnoid hemorrhage (SAH). Attempts to identify patients at highest risk of vasospasm have not led to practice change. We sought to identify patients at lowest risk of vasospasm by testing the prognostic utility of novel low risk criteria: mean MCA velocities on TCD that peaked and remained below 120 cm/s by the 7th day. Methods: Retrospective observational study of TCD values in patients admitted to The Ottawa Hospital with SAH 2018-2023. The primary outcome was presence of moderate to severe vasospasm (MCA mean velocity >160 cm/s) by day 21. Results: Data were collected on 211 patients, of whom 197 fulfilled inclusion criteria. Only 2 of 104 patients (2%) meeting our low-risk criteria developed the primary outcome, compared to 48 of 93 patients (52%) who did not meet criteria (RR 27). The Negative Predictive Value (NPV) for vasospasm in our low-risk group was 98%. Conclusions: Our low-risk criteria based on TCD patterns in the first 7 days after SAH can identify patients at very low risk of vasospasm with great accuracy. This could inform a future prospective study.

Background: Efgartigimod, a human immunoglobulin (Ig)G1 antibody Fc fragment, blocks the neonatal Fc receptor, reducing IgGs involved in chronic inflammatory demyelinating polyneuropathy (CIDP). The multi-stage, double-blinded, placebo-controlled ADHERE (NCT04281472) and open-label extension ADHERE+ (NCT04280718) trials (interim analysis cutoff: February 16, 2024) assessed efgartigimod PH20 SC in participants with CIDP. Methods: Participants with active CIDP received open-label, weekly efgartigimod PH20 SC 1000 mg during ≤12-week run-in (stage-A). Responders were randomized (1:1) to efgartigimod or placebo for ≤48 weeks (stage-B). Participants with clinical deterioration in stage-B or who completed ADHERE entered ADHERE+. Week 36 changes from run-in baseline (CFB) in adjusted Inflammatory Neuropathy Cause and Treatment (aINCAT), Inflammatory Rasch-built Overall Disability Scale (I-RODS), and grip strength scores were evaluated. Results: Of 322 stage-A participants, 221 were randomized and treated in stage-B, and 99% entered ADHERE+. Mean CFB (SE) in aINCAT, I-RODS, and grip strength scores were -1.2 (0.15) and 8.8 (1.46) and 17.5 (2.02), respectively, at ADHERE+ Week 36 (N=150). Half the participants with clinical deterioration during ADHERE stage-B restabilized on efgartigimod from ADHERE+ Week 4. Conclusions: Interim results from ADHERE+ indicate long-term effectiveness of efgartigimod PH20 SC in clinical outcomes in participants with CIDP.

Background: Efgartigimod, a human immunoglobulin (Ig)G1 antibody Fc fragment, blocks the neonatal Fc receptor, reducing IgGs involved in chronic inflammatory demyelinating polyneuropathy (CIDP), a rare, progressive, immune-mediated disease that can lead to irreversible disability. The multi-stage, double-blinded, placebo-controlled ADHERE (NCT04281472) trial assessed efgartigimod PH20 SC in participants with CIDP. Methods: Participants with active CIDP received open-label, weekly efgartigimod PH20 SC 1000 mg during ≤12-week run-in (stage-A). Responders were randomized (1:1) to weekly efgartigimod or placebo for ≤48 weeks (stage-B). This posthoc analysis evaluated changes from run-in baseline (study enrollment) to stage-B last assessment and items of the Inflammatory Rasch-built Overall Disability Scale (I-RODS). Results: Of 322 participants who entered stage-A, 221 were randomized and treated in stage-B, and 191/221 had data for run-in baseline and post–stage-B timepoints. Mean (SE) I-RODS change at stage-B last assessment vs run-in baseline was 5.7 (1.88) and -4.9 (1.82) in participants randomized to efgartigimod and placebo, respectively. 37/97 (38.1%) and 24/92 (26.1%) participants randomized to efgartigimod and placebo, respectively, experienced ≥4-point improvements in I-RODS score. Efgartigimod-treated participants improved ≥1 point in I-RODS items of clinical interest. Conclusions: Participants who received efgartigimod in stage-B experienced improvements in I-RODS score from study enrollment to stage-B last assessment.

Background: Nipocalimab is a human IgG1 monoclonal antibody targeting FcRn that selectively reduces IgG levels without impacting antigen presentation, T- and B-cell functions. This study describes the effect of nipocalimab on vaccine response. Methods: Open-label, parallel, interventional study randomized participants 1:1 to receive intravenous 30mg/kg nipocalimab at Week0 and 15mg/kg at Week2 and Week4 (active) or no drug (control). On Day 3, participants received Tdap and PPSV®23 vaccinations and were followed through Wk16. Results: Twenty-nine participants completed the study and are included (active, n=15; control, n=14). Participants with a positive anti-tetanus IgG response was comparable between groups at Wk2 and Wk16, but lower at Wk4 (nipocalimab 3/15 [20%] vs control 7/14 [50%]; P=0.089). All maintained anti-tetanus IgG above the protective threshold (0.16IU/mL) through Wk16. While anti-pneumococcal-capsular-polysaccharide (PCP) IgG levels were lower during nipocalimab treatment, the percent increase from baseline at Wk2 and Wk16 was comparable between groups. Post-vaccination, anti-PCP IgG remained above 50mg/L and showed a 2-fold increase from baseline throughout the study in both groups. Nipocalimab co-administration with vaccines was safe and well-tolerated. Conclusions: These findings suggest that nipocalimab does not impact the development of an adequate IgG response to T-cell–dependent/independent vaccines and that nipocalimab-treated patients can follow recommended vaccination schedules.

Background: Treatment-resistant obsessive compulsive disorder (trOCD) is a condition characterized by intrusive thoughts (obsessions) and uncontrollable behaviours (compulsions) unresponsive to conventional therapies. Lesioning both anterior limbs of the internal capsule is effective in ablating the circuitry underlying trOCD pathophysiology. The newest capsulotomy method is MR-guided focused ultrasound (MRgFUS). Here we measured neural networks changes of trOCD patients after MRgFUS capsulotomy using resting state functional MRI (rs-fMRI). Methods: Yale-Brown Obsessive-Compulsive Scale (YBOCS) scores and rs-fMRI data were collected in 6 trOCD patients preoperatively, postoperatively at 3-months and 1-year, along with rs-fMRI from 6 age and sex-matched controls. Independent component analysis, dual regression using the FMRIB software library, and node-node approaches were used with the CONN Toolbox. We also performed a systematic review of existing studies about trOCD resting state networks. Results: TrOCD patients demonstrated significant improvement 1-year postoperatively (mean YBOCS reduction of 41 ± 7%). Dual regression analysis 3-months postoperatively showed significantly greater sensorimotor network signal in controls compared to trOCD groups. Node-node analysis in trOCD found connectivity changed in networks associated with the cortico-striato-thalamo-cortico loop, particularly the salience and limbic networks at 1-year postoperatively. Conclusions: TrOCD patients who underwent MRgFUS capsulotomy demonstrated differences in sensorimotor and cortico-striatal connectivity and significant clinical improvement postoperatively.

Background: In the Phase 3 MycarinG study (MG0003/NCT03971422), one 6-week cycle of rozanolixizumab significantly improved myasthenia gravis (MG)-specific outcomes versus placebo. After MycarinG, patients could enrol in open-label extension studies (MG0004 then MG0007, or MG0007 directly). Methods: In MG0004 (NCT04124965), patients received once-weekly rozanolixizumab 7mg/kg or 10mg/kg for ≤52 weeks. In MG0007 (NCT04650854), after a cycle of rozanolixizumab 7mg/kg or 10mg/kg, subsequent cycles were based on symptom worsening at the investigator’s discretion. Pooled data are reported across MycarinG, MG0004 (first 6 weeks) and MG0007 (final data) for patients receiving ≥2 symptom-driven cycles (efficacy; ≤13 cycles) or ≥1 cycle (safety). Results: 196 patients received ≥1 rozanolixizumab dose of whom 129 received ≥2 symptom-driven cycles (7mg/kg: n=70; 10mg/kg: n=59). Treatment response was maintained from Cycles 1–13: mean change from baseline to Day 43 in MG-Activities of Daily Living score ranged from -3.2 to -4.9 (7mg/kg) and -3.2 to -6.7 (10mg/kg). Quantitative MG and MG Composite scores also improved. Treatment-emergent adverse events (TEAEs) did not increase with repeated cyclic treatment, and most were mild/moderate; the most common event was headache. Conclusions: Rozanolixizumab showed consistent improvements across MG-specific outcomes up to 13 cycles and repeated cyclic treatment was generally well tolerated. Funding: UCB.

Avocado is a delicious fruit crop having great economic importance. Understanding the extent of variability present in the existing germplasm is important to identify genotypes with specific traits and their utilization in crop improvement. The information on genetic variability with respect to morphological and biochemical traits in Indian avocados is limited and as it has hindered genetic improvement of the crop. In the current study, 83 avocado accessions from different regions of India were assessed for important 17 morphological and 8 biochemical traits. The results showed the existence of wide variability for traits such as fruit weight (75.88–934.12 g), pulp weight (48.08–736.19 g), seed weight (6.37–32.62 g), FRAP activity (27.65–119.81 mg AEAC/100 g), total carotenoids (0.96–7.17 mg/100 g), oil content (4.91–25.49%) and crude fibre (6.85–20.75%) in the studied accessions. The first three components of principal component analysis explained 54.79 per cent of total variance. Traits such as fruit weight, pulp weight, seed weight, moisture and oil content contributed more significantly towards total variance compared to other traits. The dendrogram constructed based on Euclidean distance wards minimum variance method divided 83 accessions into two major groups and nine sub clusters suggesting wide variability in the accessions with respect to studied traits. In this study, superior accessions for important traits such as fruit size (PA-102, PA-012), high pulp recovery (PA-036, PA-082,), thick peel (PA-084, PA-043, PA-011, PA-008), high carotenoids (PA-026, PA-096) and high oil content (PA-044, PA-043, PA-046, PA-045) were identified which have potential utility in further crop improvement programmes.

The First Large Absorption Survey in H i (FLASH) is a large-area radio survey for neutral hydrogen in and around galaxies in the intermediate redshift range $0.4\lt z\lt1.0$, using the 21-cm H i absorption line as a probe of cold neutral gas. The survey uses the ASKAP radio telescope and will cover 24,000 deg$^2$ of sky over the next five years. FLASH breaks new ground in two ways – it is the first large H i absorption survey to be carried out without any optical preselection of targets, and we use an automated Bayesian line-finding tool to search through large datasets and assign a statistical significance to potential line detections. Two Pilot Surveys, covering around 3000 deg$^2$ of sky, were carried out in 2019-22 to test and verify the strategy for the full FLASH survey. The processed data products from these Pilot Surveys (spectral-line cubes, continuum images, and catalogues) are public and available online. In this paper, we describe the FLASH spectral-line and continuum data products and discuss the quality of the H i spectra and the completeness of our automated line search. Finally, we present a set of 30 new H i absorption lines that were robustly detected in the Pilot Surveys, almost doubling the number of known H i absorption systems at $0.4\lt z\lt1$. The detected lines span a wide range in H i optical depth, including three lines with a peak optical depth $\tau\gt1$, and appear to be a mixture of intervening and associated systems. Interestingly, around two-thirds of the lines found in this untargeted sample are detected against sources with a peaked-spectrum radio continuum, which are only a minor (5–20%) fraction of the overall radio-source population. The detection rate for H i absorption lines in the Pilot Surveys (0.3 to 0.5 lines per 40 deg$^2$ ASKAP field) is a factor of two below the expected value. One possible reason for this is the presence of a range of spectral-line artefacts in the Pilot Survey data that have now been mitigated and are not expected to recur in the full FLASH survey. A future paper in this series will discuss the host galaxies of the H i absorption systems identified here.

The Australian SKA Pathfinder (ASKAP) offers powerful new capabilities for studying the polarised and magnetised Universe at radio wavelengths. In this paper, we introduce the Polarisation Sky Survey of the Universe’s Magnetism (POSSUM), a groundbreaking survey with three primary objectives: (1) to create a comprehensive Faraday rotation measure (RM) grid of up to one million compact extragalactic sources across the southern $\sim50$% of the sky (20,630 deg$^2$); (2) to map the intrinsic polarisation and RM properties of a wide range of discrete extragalactic and Galactic objects over the same area; and (3) to contribute interferometric data with excellent surface brightness sensitivity, which can be combined with single-dish data to study the diffuse Galactic interstellar medium. Observations for the full POSSUM survey commenced in May 2023 and are expected to conclude by mid-2028. POSSUM will achieve an RM grid density of around 30–50 RMs per square degree with a median measurement uncertainty of $\sim$1 rad m$^{-2}$. The survey operates primarily over a frequency range of 800–1088 MHz, with an angular resolution of 20” and a typical RMS sensitivity in Stokes Q or U of 18 $\mu$Jy beam$^{-1}$. Additionally, the survey will be supplemented by similar observations covering 1296–1440 MHz over 38% of the sky. POSSUM will enable the discovery and detailed investigation of magnetised phenomena in a wide range of cosmic environments, including the intergalactic medium and cosmic web, galaxy clusters and groups, active galactic nuclei and radio galaxies, the Magellanic System and other nearby galaxies, galaxy halos and the circumgalactic medium, and the magnetic structure of the Milky Way across a very wide range of scales, as well as the interplay between these components. This paper reviews the current science case developed by the POSSUM Collaboration and provides an overview of POSSUM’s observations, data processing, outputs, and its complementarity with other radio and multi-wavelength surveys, including future work with the SKA.

Hospital food service quality significantly impacts patient satisfaction with overall care(1) and can influence food intake, thereby increasing the risk of malnutrition(2). By contrast, meals tailored to patients’ needs result in lower complications and hospitalisation costs(3). With Australia’s ageing population and projected increases among racial and ethnic minority migrants, service delivery must adapt to promote equity and inclusion in the healthcare system. However, data is lacking on the lived experience, preferences, and acceptance of hospital food service and meal quality among older patients from culturally and linguistically diverse (CALD) backgrounds. This study aimed to bridge this gap by investigating the differences in hospital food services related to cultural and ethnic backgrounds. Semi-structured qualitative interviews were planned among 15 Australian-born and 15 CALD-background patients, aged 65 years or over, admitted to the Department of General Medicine at Flinders Medical Centre. Patients admitted with a highly contagious infectious disease (e.g., COVID-19), those referred for palliative care, receiving parenteral or enteral nutrition, or on nil-by-mouth orders were excluded. Translators were available to participants upon request. With participants’ consent, all interviews were audio recorded and transcribed verbatim. Transcripts were analysed thematically using Braun and Clarke’s six-phase process(4). Data was inductively coded with a phenomenological perspective to explore participants’ experiences with hospital food services. Similar codes were grouped together and further developed into themes through iterative discussions with the research team. The current analysis involved six participants from each group to present preliminary results. Among the 12 participants, the mean age was 82 years, ranging from 72–92 in the Australian-born group and 68–92 in the CALD group. Five primary themes emerged: (1) No Complaints—participants did not want to complain about their meals, preferring staff to focus on their healthcare. This attitude was compounded for CALD participants who lacked the language to voice complaints; (2) Food and Identity—CALD participants viewed themselves separately from Australian-born patients, with the lack of culturally familiar food contributing to a feeling of being the minority; (3) Acceptance—the food service was viewed in the context of the overall hospital system, with participants accepting that meals may not suit their preference; (4) Experiences of the Food Service—influenced by participant’s individual preferences for meal quality, menu options, and staff interactions; and (5) Nutrition and Health—All participants had a preference for smaller portions due to their perception of reduced nutritional needs, yet meals were also valued for enjoyment. These preliminary results indicate that hospital food services should offer culturally familiar options, improve patient-staff communication, and provide personalised, smaller portions to enhance patient experience. Addressing the enablers and barriers to meeting cultural and individual dietary needs in hospitals will promote equity, diversity, and inclusion in healthcare.

Claims relating to foods’ nutrition content and potential health benefits have been shown to influence consumer preferences and purchases regardless of the nutritional quality of the product(1). In Australia, permitted claims include nutrition content claims, which refer to the presence or absence of a nutrient, and health claims, which refer to health benefits of foods or nutrients in a product. Health claims include general level health claims, which refer to normal processes and functions, and high level health claims, which refer to a disease or biomarker of a disease. Products that display a health claim must meet the Nutrient Profiling Scoring Criterion (NPSC), however this is not required for products to make a nutrition content claim. The aim of this study was to examine the use of nutrition content and health claims made on Australian ready meal products and assess the proportion of products displaying claims that meet the NPSC. Analysis of the ready meal category in the 2023 FoodSwitch database, a repository of Australian food packaging images and label data for over 28,000 foods developed by The George Institute for Global Health, was conducted(2,3). Foods in the ready meal category were identified and data from the nutrition information panel was collated to calculate whether they met the NPSC. Nutrition content and health claims were extracted from product images and categorised according to claim type (nutrition or health claim) and claimed nutrient or attribute. The proportion of products meeting the NPSC was then calculated overall and by claim type (nutrition content vs health claims). Data were available for 777 ready meal products. Of these, 682 (87.8%) met the NPSC. In total, 2051 nutrition content or health claims were identified across the ready meal products, with 1909 (93.1%) of these categorised as nutrition content claims. The remaining 142 claims identified were general level health claims, with no high level health claims identified. Almost all (n = 1857, 97.3%) nutrition content claims and all general level health claims were made on products which met the NPSC. The most common claims related to protein, energy and fibre content. The use of claims was prevalent across the ready meal food category in Australia, with claims relating to nutrient content being most common. While most claims were made on products that met the NPSC, there is a need for further research to ensure the NPSC appropriately distinguishes between healthy and less healthy food products. This will ensure consumers are equipped to make informed decisions when purchasing food products.

We provide an assessment of the Infinity Two fusion pilot plant (FPP) baseline plasma physics design. Infinity Two is a four-field period, aspect ratio $A = 10$, quasi-isodynamic stellarator with improved confinement appealing to a max-$J$ approach, elevated plasma density and high magnetic fields ($ \langle B\rangle = 9$ T). Here $J$ denotes the second adiabatic invariant. At the envisioned operating point ($800$ MW deuterium-tritium (DT) fusion), the configuration has robust magnetic surfaces based on magnetohydrodynamic (MHD) equilibrium calculations and is stable to both local and global MHD instabilities. The configuration has excellent confinement properties with small neoclassical transport and low bootstrap current ($|I_{bootstrap}| \sim 2$ kA). Calculations of collisional alpha-particle confinement in a DT FPP scenario show small energy losses to the first wall (${\lt}1.5 \,\%$) and stable energetic particle/Alfvén eigenmodes at high ion density. Low turbulent transport is produced using a combination of density profile control consistent with pellet fueling and reduced stiffness to turbulent transport via three-dimensional shaping. Transport simulations with the T3D-GX-SFINCS code suite with self-consistent turbulent and neoclassical transport predict that the DT fusion power$P_{{fus}}=800$ MW operating point is attainable with high fusion gain ($Q=40$) at volume-averaged electron densities $n_e\approx 2 \times 10^{20}$ m$^{-3}$, below the Sudo density limit. Additional transport calculations show that an ignited ($Q=\infty$) solution is available at slightly higher density ($2.2 \times 10^{20}$ m$^{-3}$) with $P_{{fus}}=1.5$ GW. The magnetic configuration is defined by a magnetic coil set with sufficient room for an island divertor, shielding and blanket solutions with tritium breeding ratios (TBR) above unity. An optimistic estimate for the gas-cooled solid breeder designed helium-cooled pebble bed is TBR $\sim 1.3$. Infinity Two satisfies the physics requirements of a stellarator fusion pilot plant.